Abstract

Genetic Modifiers of Alzheimer Risk Administrative Supplement We have identified a blood biomarker signal that differentiates genetically mutant Alzheimer disease (AD)-model mice from their age- and sex-matched non-mutant littermates: markers of the cellular response to DNA damage. This supplement to the KOMP project will define the detection limits of the assay signal in time, pre-disease, and breadth of models detectable, and will examine viable knock-out mice generated in the KOMP project for signal in the blood assay as a simple screen for knock-outs with AD and pre-AD properties. This work has the potential to identify new AD risk alleles, and to produce a simple, early initial blood-based biomarker and assay for AD risk. Simple blood screens for pre-AD phenotypes could allow identification and potentially prevention of symptoms in at-risk individuals not otherwise identified.

Public Health Relevance

The purpose of this supplement to the Baylor College of Medicine Knock-Out Mouse Production and Phenotyping project (KOMP2) is to develop a promising blood-based assay for early detection of Alzheimer disease (AD) in the pre-clinical mouse model, and to screen knock-out mice generated by the KOMP2 for knock outs that predispose to AD. This work may advance early detection and prevention of AD.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
3UM1HG006348-10S1
Application #
10121529
Study Section
Special Emphasis Panel (ZHG1)
Program Officer
Fletcher, Colin F
Project Start
2011-09-28
Project End
2021-08-31
Budget Start
2020-09-11
Budget End
2021-08-31
Support Year
10
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Raghunathan, Suchi; Reynolds, Corey L; Schwartz, Robert J et al. (2018) C.B-17 SCID mice develop epicardial calcinosis with unaltered cardiac function. Fundam Clin Pharmacol :
Codner, Gemma F; Mianné, Joffrey; Caulder, Adam et al. (2018) Application of long single-stranded DNA donors in genome editing: generation and validation of mouse mutants. BMC Biol 16:70
Albrecht, Nicholas E; Alevy, Jonathan; Jiang, Danye et al. (2018) Rapid and Integrative Discovery of Retina Regulatory Molecules. Cell Rep 24:2506-2519
Moore, Bret A; Leonard, Brian C; Sebbag, Lionel et al. (2018) Identification of genes required for eye development by high-throughput screening of mouse knockouts. Commun Biol 1:236
Tanner, Mark R; Pennington, Michael W; Chamberlain, Brayden H et al. (2018) Targeting KCa1.1 Channels with a Scorpion Venom Peptide for the Therapy of Rat Models of Rheumatoid Arthritis. J Pharmacol Exp Ther 365:227-236
Morriss, Ginny R; Rajapakshe, Kimal; Huang, Shixia et al. (2018) Mechanisms of skeletal muscle wasting in a mouse model for myotonic dystrophy type 1. Hum Mol Genet 27:2789-2804
Szwarc, Maria M; Kommagani, Ramakrishna; Putluri, Vasanta et al. (2018) Steroid Receptor Coactivator-2 Controls the Pentose Phosphate Pathway through RPIA in Human Endometrial Cancer Cells. Sci Rep 8:13134
Singh, Ravi K; Kolonin, Arseniy M; Fiorotto, Marta L et al. (2018) Rbfox-Splicing Factors Maintain Skeletal Muscle Mass by Regulating Calpain3 and Proteostasis. Cell Rep 24:197-208
Lanza, Denise G; Gaspero, Angelina; Lorenzo, Isabel et al. (2018) Comparative analysis of single-stranded DNA donors to generate conditional null mouse alleles. BMC Biol 16:69
Rozman, Jan; Rathkolb, Birgit; Oestereicher, Manuela A et al. (2018) Identification of genetic elements in metabolism by high-throughput mouse phenotyping. Nat Commun 9:288

Showing the most recent 10 out of 20 publications